This invention relates to antimicrobial hydrogels and methods of preparation thereof, and more specifically, to crosslinked hydrogel networks having pendant cationic block copolymers.
Microbial adhesion onto biomaterial implants and subsequent formation of biofilm can lead to failure of the implanted devices in terms of function and structure. Among all infections found in hospitals, catheter-associated bacterial infections are the most common due to the extensive use of catheters in medical care. A 10% to 30% infection rate is reported for more than 30 million implanted urinary catheters each year in the US. Catheter infections lead to increased morbidity and mortality (up to 5% of infections) and create a multi-billion dollar burden on the US health care system because of prolonged hospital stays and increased medical costs.
In response, physically immobilizing or covalently linking antibiotics on the surfaces of catheters has been attempted to address this problem. For example, the antibiotics-coated urethral catheters have been shown to be effective in preventing catheter-associated infections in the case of short-term catheterization. However, drug resistance is easily developed with conventional antibiotics, and drug-resistant bacteria are not susceptible to the treatment of the antibiotics. An alternative approach involves coating the inner surfaces of the catheters with hydrogels or films impregnated with antimicrobial agents such as antibiotics, silver ions or iodine. Nevertheless, these antimicrobial agents and silver are highly toxic and the protection is short-lived due to the difficulty in controlling the diffusion rate.
Recently, attention has been directed to cationic polymer coatings. This is because cationic polymer coatings interact with microbial walls/membranes based on electrostatic interactions instead of targeting their metabolic activity, which is associated with the resistance. Moreover, antimicrobial polymer coatings kill or at least inhibit bacteria through active contact rather than gradually releasing toxic antimicrobial agents into the surrounding area. For example, alkylated polyvinylpyridines and alkylated polyethylenimines have been immobilized and reported to be lethal to Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). However, most antimicrobial polymers reported in the literature are non-biodegradable and non-biocompatible. Chitosan and chitosan-derivatized hydrogels/films, which are non-toxic and biodegradable, have been reported to be resistant to biofilm formation by bacteria and yeast. Nevertheless, the antimicrobial activity is not of a broad spectrum and is largely affected by the pH of the surrounding solutions. In addition, the antimicrobial agents can easily adsorb proteins, and the dead microorganisms remain on the coatings, which can trigger an immune response and inflammation, blocking the antimicrobial functional groups. More recently, UV cross-linked hydrogel made from a hydrophobic alkyl-modified quaternized ammonium chitosan grafted with poly(ethylene glycol) (PEG) was reported to have antimicrobial efficacy against Gram-positive and Gram-negative bacteria as well as fungi. However, the quality and molecular weight of chitosan vary from batch to batch, and chitosan can cause immunogenicity. Moreover, photopolymerization often produces materials with poorly controlled structure due to radical chemistry.
Therefore, an urgent need exists to develop a biodegradable and biocompatible synthetic film forming material that has strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, non-fouling properties, and can be easily applied in situ.